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Antibody to Endogenous Cardiotonic Steroid Reverses Vascular Fibrosis and Restores Vasorelaxation in Chronic Kidney Disease.
Agalakova, Natalia I; Mikhailova, Elena V; Ershov, Ivan A; Nadei, Olga V; Pyankov, Arseny A; Galagoudza, Michael M; Adair, C David; Romanova, Irina V; Bagrov, Alexei Y.
Afiliación
  • Agalakova NI; Sechenov Institute of Evolutionary Physiology and Biochemistry, 194223 St. Petersburg, Russia.
  • Mikhailova EV; Sechenov Institute of Evolutionary Physiology and Biochemistry, 194223 St. Petersburg, Russia.
  • Ershov IA; Department of Obstetrics and Gynecology, St. Petersburg State Pediatric Medical University, 194100 St. Petersburg, Russia.
  • Nadei OV; Sechenov Institute of Evolutionary Physiology and Biochemistry, 194223 St. Petersburg, Russia.
  • Pyankov AA; Sechenov Institute of Evolutionary Physiology and Biochemistry, 194223 St. Petersburg, Russia.
  • Galagoudza MM; Almazov National Medical Research Centre, 197341 St. Petersburg, Russia.
  • Adair CD; Department of Obstetrics and Gynecology, University of Tennessee College of Medicine, Chattanooga, TN 37403, USA.
  • Romanova IV; Sechenov Institute of Evolutionary Physiology and Biochemistry, 194223 St. Petersburg, Russia.
  • Bagrov AY; Padakonn Pharma, Puskini 9, 20309 Narva, Estonia.
Int J Mol Sci ; 25(16)2024 Aug 15.
Article en En | MEDLINE | ID: mdl-39201581
ABSTRACT
Marinobufagenin (MBG) is implicated in chronic kidney disease, where it removes Fli1-induced inhibition of the collagen-1. We hypothesized that (i) in nephrectomized rats, aortic fibrosis develops due to elevated plasma MBG and inhibited Fli1, and (ii) that the antibody to MBG reduces collagen-1 and improves vasodilatation. A partial nephrectomy was performed in male Sprague-Dawley rats. Sham-operated animals comprised the control group. At 5 weeks following nephrectomy, rats were administered the vehicle (n = 8), or the anti-MBG antibody (n = 8). Isolated aortic rings were tested for their responsiveness to sodium nitroprusside following endothelin-1-induced constriction. In nephrectomized rats, there was an increase in the intensity of collagen staining in the aortic wall vs. the controls. In antibody-treated rats, the structure of bundles of collagen fibers had ordered organization. Western blots of the aorta had lower levels of Fli1 (arbitrary units, 1 ± 0.05 vs. 0.2 ± 0.01; p < 0.001) and greater collagen-1 (arbitrary units, 1 ± 0.01 vs. 9 ± 0.4; p < 0.001) vs. the control group. Administration of the MBG antibody to rats reversed the effect of the nephrectomy on Fli1 and collagen-1 proteins. Aortic rings pretreated with endothelin-1 exhibited 50% relaxation following the addition of sodium nitroprusside (EC50 = 0.28 µmol/L). The responsiveness of the aortic rings obtained from nephrectomized rats was markedly reduced (EC50 = 3.5 mol/L) compared to the control rings. Treatment of rats with the antibody restored vasorelaxation. Thus, the anti-MBG antibody counteracts the Fli1-collagen-1 system and reduces aortic fibrosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasodilatación / Fibrosis / Bufanólidos / Ratas Sprague-Dawley / Insuficiencia Renal Crónica Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasodilatación / Fibrosis / Bufanólidos / Ratas Sprague-Dawley / Insuficiencia Renal Crónica Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Suiza